Cancer is the second leading cause of death in the United States. Although “cancer” is used to describe many different types of cancer, i.e., breast, prostate, lung, colon, pancreas, each type of cancer differs both at the phenotypic level and the genetic level. The unregulated growth characteristic of cancer occurs when the expression of one or more genes becomes dysregulated due to mutations, and cell growth can no longer be controlled.
Genes are often classified in two classes, oncogenes and tumor suppressor genes. Oncogenes are genes whose normal function is to promote cell growth, but only under specific conditions. When an oncogene gains a mutation and then loses that control, it promotes growth under all conditions. However, it has been found that for cancer to be truly successful the cancer must also acquire mutations in tumor suppressor genes. The normal function of tumor suppressor genes is to stop cellular growth. Examples of tumor suppressors include p53, p16, p21, and APC, all of which, when acting normally, stop a cell from dividing and growing uncontrollably. When a tumor suppressor is mutated or lost, that brake on cellular growth is also lost, allowing cells to now grow without restraints.
APCDD1 (also known as B7323, B7323N, DRAPC1 and FP7019) is a polypeptide whose expression is downregulated by the tumor suppressor gene, adenopolyposis coli (APC) (Takahashi et al., Cancer Research 62: 5651-5656, 2002). APCDD1 appears to be up-regulated in colon cancer. Overexpression of APCDD1 in a colon cancer cell line has been shown to stimulate cell growth in vitro and to moderately increase tumor growth in vivo.
To date, however, the role of APCDD1 in cancer and other diseases and disorders has not been fully elucidated. Accordingly there is a need to identify compositions and methods that modulate APCDD1. The present invention is directed to these, as well as other, important needs.